KR20180061362A - Endless core-cis fiber based hyaluronan or C11-C18 acylated derivatives thereof, process and use of the fiber, staple fiber made from the fiber, yarn and textile, and uses thereof - Google Patents

Abstract

The present invention relates to a two-component biodegradable core comprising a combination of native hyaluronan and a C ₁₁ -C ₁₈ acylated hyaluronan or a combination of C ₁₁ -C ₁₈ acylated hyaluronan, ≪ / RTI > core-sheath fibers. Furthermore, the present invention relates to a process for its preparation and its use, in particular for the controlled release of active agents. The fibers may be further processed in the form of staple fibers, yarns, braided, woven, knitted and nonwoven textiles.

Description

Endless core-cis fiber based hyaluronan or C11-C18 acylated derivatives thereof, process and use of the fiber, staple fiber made from the fiber, yarn and textile, and uses thereof

The present invention relates to a biodegradable endless core-cis fiber comprising a combination of native hyaluronan and a C ₁₁ -C ₁₈ acylated hyaluronan or a combination of C ₁₁ -C ₁₈ acylated hyaluronan endless core-sheath fiber) and a method of making the same. The preparation of the fibers is carried out using wet spinning to obtain endless monofilaments having a core-cis structure followed by monofilament processing using everyday textile techniques to produce linear textile yarn or braided thread), flat textile (woven textile, knitted textile, braided textile, nonwoven textile) and tubular structure (e.g., Braided, woven, knitted).

The biodegradable fibers produced comprise two components, core and cis, which can have two completely different functions, while at the same time they can carry completely different activators, lt; RTI ID = 0.0 > fibers. < / RTI > Applicable uses of these fibers are in medicine, especially surgical materials, tissue engineering and controlled release systems.

A possible technique for processing hyaluronic acid into a fiber form is the wet spinning method described for hyaluronic acid in the international application WO 2009/050389. Fibers are obtained by coagulation in a concentrated acetic acid (80% to 90%) bath, followed by drying and drawing. Fibers made from native hyaluronan are very water soluble, but this is disadvantageous in many applications. In order to reduce the solubility of the fibers, the authors mention that the fibers can be coated with hydrophobic agents of plant or animal origin.

In addition, patent document WO2013167098 (A2) uses acetic acid (1% to 99%) for fiber production but contains alcohol (1 to 99%) in the mixture to add higher strength to the fibers.

The patents CZ 304303 and CZ 304266 use similar techniques and solidification baths (organic acids + lower alcohols) necessary to obtain fibers based on hyaluronic acid. However, they still only obtain simple fibers which are not suitable for use in the controlled release of active agents because they do not have a core-cis arrangement and are unable to release native HA and optionally other active compounds. Furthermore, CZ 304266 describes fibers made from oxidized hyaluronan at position 6 on the N-acetyl-D-glucosamine part, which are derivatives with different properties. These fibers show longer term stability in the wet environment than the original hyaluronic acid derived fibers, but only for about 30 minutes, after which they lose their fiber shape and turn into gel. Fibers are not primarily identified as carriers of active agents.

In the detailed description of patent CZ304303, simple fibers and textiles based on hydrophobized HA are described. Even if these fibers are swollen, they can not provide direct and controlled release of the native HA or active agent at the application site.

Patent documents WO 93/11803, WO 98/08876, US 5658582, US 2004/0192643 describe the formation of fiber and nonwoven textiles from esters of hyaluronic acid. The spinning technique used can form short fibers but not endless filaments. The length of the fibers varies from 5 to 100 mm, and the fibers can only be processed in non-woven textile form.

For the application of fibers made from esters of hyaluronan, staple fibers in the form of non-woven textiles are described (US 5658582), staple fibers are used for the production of gauze, sealing material, net, 98/08876, US 006632802), or the manufacture of wound dressing materials (WO 2007/003905).

Patent document WO 2010028025 describes fibers of hyaluronic acid and its derivatives (especially salts), their preparation and use options (wrinkles filling, controlled release of drugs, surgery). Fibers are obtained by crosslinking hyaluronic acid or derivatives thereof with 1,4-butanediol diglycidyl ether (BDDE). These are also simply fibers.

The following patent documents relate to the preparation of core-cis fibers prepared using a wet spinning process.

U.S. Patent No. 8062654 describes gel or hydrogel core-cis fibers. Based material is two polymeric materials, wherein the polymer of the core is a polymeric gel with a potential content of a cationic cross-linker. Other biodegradable materials that form cis are good in solubility in chlorinated solvents which are miscible with a lipid solvent (pentane, hexane) used as a coagulation (spinning) bath. The fibers of the fibers are made of lactic acid, polycaprolactone, polymers of polyglycolic acid, or copolymers and mixtures thereof. The core of the fiber is made of an alginate that is crosslinked by the addition of CaCO ₃ .

Patent document US 2012/0040463 describes the preparation of hollow / multi-membrane fibers from fiber-forming solutions of polysaccharides or collagen using wet spinning techniques. The manufacturing principle is for repeatedly layering and coagulating polymeric materials onto the fibers. In the detailed description of the document, it is stated that the periodic solidification technique is suitable for materials which are difficult to be deformed into the shape of endless fibers, such as chitosan, hyaluronic acid, alginate, carboxymethylcellulose, collagen.

Patent document US 6162537 describes two component fibers, wherein one component is a reabsorbable polymer and the other component is made of a material that is capable of forming fibers but is not reabsorbable. This relates to polyesters, polyamides, polyolefins and polyurethanes, in particular polypropylene (PP), polyethylene (PE), polyhexamethylene terephthalate (PBTP). One or more of the ingredients contain a pharmacologically active ingredient. The use of such materials is aimed at the area of nondegradable implantable medical devices. However, such an implant is only identified for applications where complete decomposition and reabsorption of the implant need not be required.

The most frequently described core-sheath fiber preparation procedure is the spinning of the melt, referred to as melt spinning technique. In this way, core-sheath fibers were produced in U.S. Pat. No. 8,124,949 or in U.S. Patent Application Serial No. 2011/0028062. The melt spinning technique is possible only through the spinning of the meltable polymer, which can not be used in the case of the subject matter of the present invention.

Patent document WO 2004/061171 describes fibers of the " side by side " type, where there are two polymeric materials with different properties, but due to the arrangement of the two components in the fibers, This structure can not be used when the activator dispersed in one polymer component must be coated with a protective sheath layer.

Patent document WO 2006/102374 describes healing netting of two component core-cis fibers, wherein only bioactive agents are contained in the sheath. The two component fibers do not contain an absorbent core and an absorbent surface. The polymeric material of the sheath is selected from the group consisting of polylactide, polyglycolide, p-dioxane, poly (trimethylene carbonate), polycaprolactone, polyorthoester. Suitable polymeric materials for the core are selected from the group consisting of polyesters, polyolefins, polyamides and fluorated polymers. The disadvantage of these fibers or nets is that they contain only the bioactive agent in the fiber's cis, which excludes protective and controlled release of the fiber.

Hyaluronidase shortcomings of the art are I or a C ₁₁ -C ₁₈ Ah one based on the acylated derivative endless core - is solved by a fiber sheath, its subject is a combination thereof or of the I and its Oh the acylated derivatives with hyaluronic Wherein the core and sheath of the fiber are in any of the following arrangements: < RTI ID = 0.0 >

A) the core comprises hyaluronic acid or a salt thereof, wherein the cis comprises C ₁₁ -C ₁₈ acylated hyaluronan;

B) the core comprises C ₁₁ -C ₁₈ acylated hyaluronan, wherein the sheath comprises hyaluronic acid or a salt thereof;

C) a core is C ₁₁ -C ₁₈ Ah comprises I to the acylated hyaluronic, sheath difference is different from a C ₁₁ -C ₁₈ ah acylated hyaluronic the core I and the C ₁₁ -C ₁₈ C ₁₁ -C ₁₈ acyl The degree of substitution of the C ₁₁ -C ₁₈ acylated hyaluronan in the cis is the same as or different from the substitution of the C ₁₁ -C ₁₈ acylated hyaluronan in the core; or

D) core comprises a C ₁₁ -C ₁₈ acylated hyaluronan, wherein the sheath comprises a different C ₁₁ -C ₁₈ acylated hyaluronan, which differs in the degree of substitution from the C ₁₁ -C ₁₈ acylated hyaluronan of the core Includes Ronan.

The options of core-cis array components in terms of their material composition are shown in Table 1.

Table 1. Options for the arrangement of core-cis fiber components of the present invention.

The fiber of the present invention comprises two components, the core comprising hyaluronic acid or a salt thereof or a C ₁₁ -C ₁₈ acylated hyaluronan, wherein the sheath comprises hyaluronic acid or a salt thereof or C ₁₁ -C ₁₈ acyl It contains true hyaluronan. If containing a fiber core and fiber sheath are both C ₁₁ -C ₁₈ Oh I with hyaluronic misfire of the present invention, C ₁₁ -C ₁₈ ah as the misfire hyaluronic I are the chemical structures are different. The difference is made up of different substitution classes of C ₁₁ -C ₁₈ and / or different substitutions.

When the fiber of the invention of the arrangement C applies, as a sheath is C ₁₁ -C ₁₈ ah acylated hyaluronic the core I and the C ₁₁ -C ₁₈ acyl is the difference I has a different C ₁₁ -C ₁₈ oh the acylated hyaluronic , While the substitution degree thereof is the same as or different from the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan of the core.

When the inventive fibers of the D arrangement are applied, the sheath contains different C ₁₁ -C ₁₈ acylated hyaluronan with different degrees of substitution with the C ₁₁ -C ₁₈ acylated hyaluronan of the core, The types of C ₁₁ -C ₁₈ substituents are the same.

The C ₁₁ -C ₁₈ acylated hyaluronan is preferably acylated in the primary alcohol of N -acetyl-glucosamine.

The molar mass of the C ₁₁ -C ₁₈ acylated hyaluronan in the core and / or the cis in the fiber arrangement of the present invention is in the range of 1 × 10 ⁵ to 7 × ^{10 5} g / mol, preferably in the range of 2 × 10 ⁵ to 3 × 10 ⁵ g / mol to be.

According to a preferred embodiment of the present invention, the C ₁₁ -C ₁₈ acylated hyaluronan is selected from the group consisting of palmitoyl hyaluronan, stearoyl hyaluronan, or oleyl hyaluronan.

According to a preferred embodiment, the hyaluronic acid and / or salt, while molar mass of the compound are in the range of 1x10 ⁵ to 2x10 ⁶ g / mol, preferably 8x10 ⁵ to 1.8x10 ⁶ g / mol, salts of hyaluronic acid Alkali metal ions, alkaline earth metal ions, preferably Na ⁺ , K ⁺ , Ca ²⁺ or Mg ²⁺ .

According to another preferred embodiment of the present invention, the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan in the sequence A or the sequence B ranges from 5% to 80%, preferably 30% to 60%. Furthermore, the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the core of the array C is in the range of 5% to 80%, preferably 5% to 29%, more preferably 10% to 20% , And the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the arrangement C is in the range of 5% to 80%, preferably 30% to 80%, more preferably 40% to 60%. Furthermore, the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the core of the array D is 5% to 29%, preferably 10% to 20%, and the degree of substitution of the C _11- The substitution degree of the C ₁₈ acylated hyaluronan ranges from 30% to 80%, preferably from 40% to 60%.

Both of the fiber components of the present invention may preferably contain one or more active agents. According to a preferred embodiment of the fibers of the present invention, the core and sheath contain both one or more of the same or different activators. The fibers may then contain completely different active agents that can be released at different rates depending on the location of the active agents in the fiber component of the present invention. The active agent is selected from the group consisting of an antimicrobial agent, a disinfectant, an antibiotic, an anti-inflammatory agent, a hemostatic agent, an anesthetic agent, a cytostatic agent, a hormone, an immunomodulating agent, an immunosuppressant or contrast agent, preferably a magnetic nano-particle or a fluorescent agent. The active agent may also be incorporated into the micelle and passed into the fiber core.

In a combination of native HA and acylated HA, the fibers may be arranged in a core made of native hyaluronan and a sheath made of C ₁₁ -C ₁₈ acylated hyaluronan, or the core may be C ₁₁ -C ₁₈ acylated hyaluronan and arranged in a reverse arrangement when the sheath is made of native hyaluronan, which is referred to as " reverse fiber ". In the fiber, there is a combination of a water soluble component (native HA) and a hydrophobic component (acylated HA), which shows reduced solubility or, in other words, higher stability in an aqueous environment.

When the fiber core of the present invention is made from native hyaluronan and the fiber sheath is made from acylated hyaluronan, the fiber sheath fills the protective function associated with the fiber core according to the invention. The sheath ensures mechanical protection of the core during textile processing and also assures protection from aggressive environments that can lead to fiber breakup and premature release of the original hyaluronan or too rapid release, ≪ / RTI >

In the case of a reverse arrangement, the fibers of the present invention act as fiber cores containing acylated hyaluronan as a reinforcing component which ensures the mechanical cohesion of the fibers, and finally the textiles produced, even after contact with liquids such as water or body fluids do.

Another fiber arrangement option is the combination of two hyaluronan derivatives acylated using two different C ₁₁ -C ₁₈ fatty acids on the hydroxyl group of the hyaluronan. The fiber core is preferably made of oleyl hyaluronan, and the fiber sheath is made of palmitoyl hyaluronan.

A different fiber arrangement option is the combination of two hyaluronan derivatives which are acylated using the same C ₁₁ -C ₁₈ fatty acids on the hydroxyl groups of the hyaluronan but differ in the degree of substitution. The fiber cores are preferably made of palmitoyl hyaluronan having a degree of substitution of 5% to 29%, and the fibrous sheath is made of palmitoyl hyaluronan having a degree of substitution of 30% to 80%. In this preferred arrangement, the hydrophobic sheath provides mechanical protection of the core and protection against aggressive environments during textile processing, while the core is only slightly hydrophobic due to its low degree of substitution, so that it can carry the active agent.

According to a preferred embodiment of the present invention, the fineness of the fiber is in the range of 10 to 40 tex, preferably 15 to 35 tex, more preferably 22 to 28 tex, the core: sheath volume ratio is 3: 1 To 1: 6, preferably 1: 3 to 1: 5, more preferably 1: 4. The cross-section of the fibers of the present invention has an irregular shape, which is typical for fibers made using the wet spinning process (see FIG. 1A). The corresponding fiber intersection values for the various fiber finenesses are shown in Table 2. The tensile strength of the fibers is in the range of 0.8 to 3.5 N and the breaking elongation is in the range of 8% to 30%.

Table 2. Values of the corresponding diameters of the fibers of the present invention for various fineness values.

The fibers of the present invention are preferably used in the production of yarns, braided textiles, woven textiles or knitted textiles.

Applicable uses of the core-cis fiber of the present invention are in the area of controlled release systems of medicaments, especially surgical materials, tissue engineering and activators.

The component arrangement in the fibers of the present invention is preferably centrally located and is shown in Fig. 1A where the fiber core is located in the center of the sheath. In Figure 1a, the fibers of the present invention in which the core is exposed are shown where the sheath does not cover the core in one section of the fiber. However, the fibers produced according to the method of the present invention provide monofilaments, i.e., the endless core-cis fibers of the present invention, wherein the sheath covers the core throughout its length.

The core-cis fiber of the present invention is produced using a wet spinning technique. This technique is a gentle technique for polymers that degrade at high temperatures. At the same time, it is possible to use an activator which is unstable at high temperature and which is decomposed or decomposed into a polymer solution spun using this technique, and it is possible to obtain a fiber containing this activator. The disadvantage of incorporating the active agent into the simple fibers can be the elution of the active agent through a diffusion process during fiber coagulation. This disadvantage can be attenuated or halted by the core-sheath structure, which ensures that the cis is functioning as a barrier so that the active compound is not eluted into the coagulation bath.

The method of making the core-cis fiber of the present invention is based on the preparation of two different spinning solutions of a hyaluronan-based polymer, and subsequently a separate process of simultaneous spinning of these fibers using a coaxial spinneret Manufacturing.

In one embodiment of the method of the present invention for fiber spinning in array A or array B, a first spinning solution containing intrinsic hyaluronan in demineralized water in a concentration range of 1 to 8 wt.%, A second spinning solution containing a C ₁₁ -C ₁₈ acylated hyaluronan in a concentration range of 2 to 8% by weight in a mixture of demineralized water is separately prepared, wherein the water content is from 30 v / v% And the lower alcohol content is in the range of 10 v / v% to 70 v / v%. Subsequently, the first spinning solution and the second spinning solution together are mixed with 2 to 40% by weight of organic acid , Preferably lactic acid, at least 50% by weight of a lower alcohol, preferably ethanol, propan-1-ol or propan-2-ol and 2 to 48% by weight of water, B fibers, which are further washed with a lower alcohol, and then dried.

In another embodiment of the method of the present invention for the fiber spinning of array C or array D, a C ₁₁ -C ₁₈ acylated hyaluronan in a mixture of water and a lower alcohol is present in a concentration range of 2 to 8% a first spinning solution, and to prepare a second spinning solution containing water and ₁₈ different C ₁₁ -C lower alcohol in the mixture of the O concentration range of I to the acylated hyaluronic 2 to 8% by weight individually, wherein a, The water content in both solutions ranges from 30 v / v% to 90 v / v% and the lower alcohol content ranges from 10 v / v% to 70 v / v% The second spinning liquid together with 2 to 40% by weight of an organic acid, preferably lactic acid, 50% by weight or more of a lower alcohol, preferably ethanol, propan-1-ol or propan- Extruding into a coagulating bath containing water to form fibers of arrangement C or arrangement D, Further wash with lower alcohol then dry.

Preferably, the first spinning solution and / or the second spinning solution, while carrying out the method of the present invention, contains an acylated hyaluronan-based nano-micelle composition containing, or containing, do.

In terms of molar mass, a suitable ratio of native hyaluronan ranges from 1 x 10 ⁵ to 2 x 10 ⁶ g / mol. The molar mass ratio of the acylated hyaluronan used ranges from ¹ x ^{10 5} to 7 x 10 ⁵ g / mol, preferably from 2 x 10 ⁵ to 3 x 10 ⁵ g / mol. The substitution degree (acylation degree) of the C ₁₁ -C ₁₈ acylated hyaluronan to the fiber array A or the array B of the present invention is in the range of 5 to 80%, preferably 30 to 60%. Furthermore, the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the core of the array C is in the range of 5 to 80%, preferably 5 to 29%, more preferably 10 to 20% The substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the sheath of C ranges from 5 to 80%, preferably from 30 to 80%, more preferably from 40 to 60%. Further, the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the core of the sequence D is 5 to 29%, preferably 10 to 20%, and the substitution degree of the C ₁₁ -C ₁₈ The degree of substitution of the acylated hyaluronan ranges from 30 to 80%, preferably from 40 to 60%.

The low molecular weight alcohols for the first and / or second spinning solution are preferably selected from the group consisting of methanol, ethanol, propan-1-ol or propan-2-ol.

As described above, the prepared spinning liquids are extruded into a coagulation bath through spinning projections which are co-axially aligned with each other. The coaxial spinning protrusion is composed of an inner spinning protrusion having a circular section and an outer spinning protrusion having an annular section. When the core-cis fiber of the present invention is formed, the spinning liquid forming the fiber core of the present invention is extruded through the inner spinning projections, and the spinning solution forming the fiber sheath of the present invention is extruded through the outer spinning projections. The fibers obtained are further washed in a bath of lower alcohols, preferably ethanol, propan-1-ol or propan-2-ol, and air dried in a natural air or at a slightly elevated temperature Lt; / RTI > The described methods of making fibers and the range of spinning conditions also apply to all variant arrangements of component arrangements within the core-cis fiber of the present invention. The core-cis fiber of the present invention produced by the present invention can be produced by a common textile technique such as linear textile (twisted yarn or braided yarn), flat type textile (woven textile, knitted textile, braided textile, non-woven textile) Can be further processed into the shape of a tubular structure (braided, woven, knitted).

The above-described method of the present invention is characterized in that the core is made of the original hyaluronan and the fiber made of acylated hyaluronan, or the core is made of acylated hyaluronan and the cis is the original hyaluronan &Quot; reverse " fibers made with < / RTI > Reverse fibers are converted into biocompatible gels when the hyaluronic acid in the fibers is contacted with the wet environment and then increase the bioacceptance of the entire fiber conjugate while at the same time reducing the inherent hyaluronan release, Characterized in that the release of the active agent is delayed at the site of application if it is contained in the cis. When such fibers are processed in the form of a textile, after the fibers are contacted with an aqueous medium (e.g. water or body fluid), a gel compact layer of hyaluronan filling pores in the textile is formed, The actual hyaluronan core ensures the mechanical cohesion of the textile. Thus, the fibers develop into a sealed composite textile structure filled with gel, and can be used, for example, as an anti-adhesive device to form a barrier and prevent undesirable adsorption of tissue or organ.

The core-cis fibers of the present invention may be combined with a water-soluble and insoluble (swellable) part (depending on the core and sheath composition), or hydrophobic and / or hydrophobic, depending on the C ₁₁ -C ₁₈ acylated hyaluronan used and its degree of substitution Are combined with two insoluble constituents which may differ in their degree of swelling. Fibers are biodegradable and are therefore gradually degraded and absorbed in living organisms.

The range of desirable geometric characteristics of the fibers mentioned above depends in part on the trouble-free spinning process and in part on the processability of the textile technology. In order to ensure continuous fiber formation without rupture, an increased fineness value is more preferred. In the case of a textile process, it is better to use such fibers because finer fibers are more flexible, but at the same time, the width of the sheath must be sufficient to prevent rupture of the sheath through friction by the operating elements of the machine It is necessary to hold it. Within the desired fineness and core: sheath volume ratio used, the satisfactory mechanical resistance of the fibers required for textile processing is ensured.

The fibers of the present invention may be used in endless fiber form or in staple fiber form for further textile processing. The staple fibers can be made by cutting or tearing the endless fibers of the present invention such that the length of the short section is from 3 to 150 mm, preferably from 50 to 90 mm.

The endless fiber of the present invention can be processed into a spun yarn form. The yarns may be made in the form of single fibers in the form of untangled monofilaments, or in bundles containing 2 to 10, preferably 3 to 6 such fibers. The fineness of the yarn may range from 10 to 400 tex, preferably from 30 to 100 tex. The yarns of the present invention made of fiber bundles preferably contain at least one twist per 1 m in length to form a twisted bundle.

The yarns, that is, the twisted bundles of bundles or fibers of the single fibers (monofilaments) or parallel oriented fibers of the present invention can be processed by braiding, knitting or weaving. The staple fibers can be processed into non-woven textiles, preferably needle-punched or stitch-bonded textile. The braided, woven, knitted or nonwoven textiles of the present invention are applicable to the fields of medicine, tissue engineering and controlled release systems.

According to another embodiment of the present invention there is provided a yarn made of two or more fibers wherein the one or more fibers are the inventive fibers as described above and the one or more fibers are fibers of other biodegradable materials Wherein the biodegradable material is selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), copolymer of polylactic acid and polyglycolic acid (PLGA), polycaprolactone (PCL) (PDA) or polyhydroxyalkanoate (PHA), preferably polylactic acid (PLA), or a copolymer of polylactic acid and polyglycolic acid (PLGA). It is also possible to use fibers of an inert material selected from the group consisting of polyethylene (PE), polypropylene (PP), polyetherester (PEE), polyamide (PAD) or polyester (PES).

The fineness of the yarn made of the fibers of the present invention is in the range of 10 to 400 tex, preferably 30 to 100 tex. Spun yarns are commonly used in the art to form textiles that are linearly braded textile (braided yarn), flat (braided band), or tubular (braided), and finally non-circular, Can be used and can be braided using known techniques. The characteristics of the textile structure depend on the method of interlacing fibers or yarns, i.e. the technical setting of the braiding process.

According to a preferred embodiment of the present invention, the fibers of the present invention contain one or more yarns of the present invention, while one or more fibers are present in component arrangement A, B, C or D as defined above, Can be produced.

Breded textile can be made from 3 to 96 yarns of the present invention. Processing on a flat braiding machine produces a narrow flat braided textile with band characteristics. Processing on a circular braiding machine produces a braided textile with a cross-section of the major circle, which may be a commutated or tubular, i.e., tubular with a hollow in the center. When a braided textile produced from 3 to 11 yarns of the present invention, preferably 3, 4, or 8 yarns, is produced by a circular braiding machine, it has the property of a thread with a compact cross section . A textile made of 12 to 96 yarns, preferably a yarn having a number of yarns of a multiple of 4, more preferably 12, 16, 24, 32 or 48 yarns, a braided textile having a tubular structure, Is to be produced by a circular braiding machine. One or more filled fibers may be inserted into such hollow using conventional techniques during braiding. If the hollow volume is not fully filled with filler fibers, the cross-section of the braided textile retains the tubular features. When the hollow volume is completely filled with filled fibers, the cross-section of the braided textile will have a compact character. Filled fibers can be inserted along the yarn within a textile braid made of eight yarns, likewise using conventional techniques during braiding on a circular braiding machine. The cross section of such a braided textile also has a compact feature.

The filled fibers may be in the form of a yarn of the present invention, a yarn of staple fiber origin, or a braided yarn. The diameter of the filled fibers, or the corresponding diameter, is in the range of 0.0001 to 1 mm, preferably 0.01 to 0.1 mm.

When it is desired to reach the " burst effect " of the sheath as described below, the cross-section of the braided textile is preferably compact.

The filled fibers may be selected from the group consisting of hyaluronic acid or derivatives thereof, polylactic acid (PLA), polyglycolic acid (PGA), copolymers of polylactic acid and polyglycolic acid (PLGA), polycaprolactone (PCL), polydioxanone May be made of a biodegradable polymer selected from the group consisting of polyhydroxyalkanoate (PHA), preferably polylactic acid (PLA) or a copolymer of polylactic acid and polyglycolic acid (PLGA). Non-resorbable biocompatible polymers can be used, for example, as polyethylene (PE), polypropylene (PP), polyetherester (PEE), polyamide (PAD) (PES).

Another option for processing yarns of the present invention is through weaving. Weaving is understood to produce a woven flat textile by crossing one or more longitudinal (warp) sets of yarns and one or more lateral (weft) sets of yarns in a weaving loom in a direction perpendicular to each other. The warp and weft yarns are each understood to be the single fibers of the present invention, the bundles of these fibers oriented in parallel, or the twisted bundles of these fibers.

A further option for processing yarns of the present invention (single fibers, bundles of parallel fibers or bundles of twisted fibers) is through knitting. Knitting is the manufacture of knitted flat or tubular textiles by shaping the yarns of the present invention in wale and course order with intermeshed loops interlaced with each other, optionally using other knit elements I understand. The knitted flat or tubular textile can be one or more of cross-section, double-side or double-weft yarn-knitted textile or single or double-sided warp-knitted textile, preferably tricot-knit, twill- A satin-knit fabric, or a knit fabric with an inlaid weft yarn. Spun yarns are understood as single fibers of the present invention, bundles of parallel oriented fibers, or twisted bundles of these fibers.

The core and the sheath of the fiber in the yarn are present in the arrangement A, C or D, and in the case of the arrangement A, the degree of substitution of the C ₁₁ -C ₁₈ acylated hyaluronan in the sheath is 30 to 80%, preferably 40 to 60 %, And in the case of the arrangement C or the arrangement D, the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan in the core is in the range of 5 to 29%, preferably 10 to 20%, and the degree of substitution of C ₁₁ -C ₁₈ Linear, flat or tubular textiles made from the fibers of the present invention having a degree of substitution of hyaluronan in the range of from 30 to 80%, preferably from 40 to 60%, are used for the controlled release of HA Can be used for the synergistic effect of textile weave and swelling of the fiber. When the textile comes into contact with a liquid preparation, such as water or body fluids, fiber swelling occurs, resulting in mechanical stresses on the fibers and subsequent rupture of the core-sheath type fiber sheath structure "). The resulting rupture consists of an acylated hyaluronan with native hyaluronan, eventually having a degree of substitution of 5 to 29%, preferably 10 to 20%, and optionally an active agent (such as a pharmaceutical preparation or an inorganic particle) If present in the fiber core, allows controlled release thereof. This is illustrated in Figures 2a and 2b. Figure 2a shows the inventive early graded textile fabric made from the core-cis fiber of the present invention, Figure 2b shows this textile after being soaked in water, flowing down the core and then drying; The collapsed fibrous sheath showing localized rupture can be well observed, while the fibers flow from the core to the soluble hyaluronan and have a flat structure. In the fibers of the present invention, even with a single non-braided / knit / woven fiber, fiber bundle or twisted fiber bundle, due to the small width of the sheath when the volume ratio of core to sheath is in the range of about 3: 1 to 1: , And a " bursting effect " upon swelling may occur. Otherwise, this effect occurs only when the fibers of the present invention are processed in the form of a braided, woven or knitted textile because the pressure build-up in swelling occurs in the textile structure and through this pressure the fibrous sheath of the present invention is torn . Surprisingly, upon swelling of the braided, woven or knitted textile of the present invention, only a partial seam of a single fiber sheath occurs, and the textile structure remains compact despite the many interferences. No significant swelling to the incoherent gel occurs and no textile structure disintegration to a single fiber occurs, but the textile structure is maintained as shown in FIG. 2B.

In the case of a braided textile, a structure rupture effect occurs at a braiding angle of at least 20 °, preferably at least 25 °, while the fineness of the yarn is x tex as mentioned in Table 3 below The braiding density of the yarn yarn is not less than y cm ^-1 , preferably not less than z cm ^-1 .

Table 3. Braiding density required to reach " rupture effect " for yarns of different fineness

The braiding angle is understood as an angle formed between the longitudinal axis of the braided textile and the spinning yarn, or as a half angle between the yarns interlaced with respect to the braiding direction.

The braiding density can be a continuous spinning transition (from tubular textile) from the face to the back (in a flat textile), or from an outer to an inner surface per 1 cm of the length of the braided textile, . ≪ / RTI >

The upper limit of the brazing angle is 45 [deg.], And the braiding density is limited by the workability and limit geometrical characteristics of the braided structure.

Other parameters of the braided textile:

Tubular braided textile diameter or braided yarn diameter: 0.3 to 15 mm

Flat Braided Textile Width: 0.3 to 15 mm

Number of braided yarns in textile: 3 to 96 yarns.

Spinning fineness range: 10 to 400 tex, preferably 30 to 100 tex.

The number of filled fibers forming the filling of the tubular structure due to the braiding of at least eight yarns: 1 to 1000.

Diameters of the fibers / fibers forming the fill of the tubular braided textile: 0.0001 to 1 mm, preferably 0.01 to 0.1 mm.

In order to ensure the " rupture effect " of the inventive fibrous sheath in the woven textile of the present invention, as set forth in Table 4 below, when the yarn fineness is a tex, the fabric set is at least b cm ^-1 , it is necessary to apply not less than c cm ^-1. The fabric set is understood as the number of warp or weft spun yarns per 1 cm width of the woven textile. Preferably, plain weave or twill can be used.

The upper limit of the fabric set is limited by the spinning processability and the limiting geometry of the woven structure.

The yarn fineness is in the range of 10 to 400 tex, preferably 30 to 100 tex.

Table 4. Fabric set required to reach "burst effect" for yarns of various finenesses

In order to ensure the " rupture effect " of the inventive fibrous sheath in the knitted textile of the present invention, when the yarn fineness is e tex, the colum density is f dm ^-1 Or more, preferably g dm ^-1 or more. The wale density is understood as the number of wales per cm of width of the knitted textile.

The upper limit of the wale density is limited by the spinning processability and the limit geometry of the nitride structure.

The yarn fineness is in the range of 10 to 400 tex, preferably 30 to 100 tex.

Table 5. Column density of the links of the braded textile that is needed to reach the "burst effect" for the yarns of different fineness.

When the inventive braided linear, flat or tubular textile (thread, band, tube) with parameters of the textile having a " bursting effect " during weaving or knitting is used, this is the structure of the woven or braided flat textile , Since the burst effect is ensured by the braided linear, flat or tubular textile of the present invention with the textile parameter of the " burst effect ", and is therefore also expressed in woven or knitted textile with the open features of the mesh It will be.

Controlled release

The sheath is made of acylated HA having a degree of substitution of 30% to 80%, preferably 40% to 60%, and the core is made of native HA or 5% to 29%, preferably 10% to 20% In textiles made from core-cis fibers of the present invention made with acylated HA with degree of substitution, it is possible to regulate the path of core release, thereby selectively controlling the release of active agents contained in the fibers Things are also possible. It is also possible to regulate the start of release, the release rate, the total duration of release, the amount of release agent, and in the case of flat and tubular textiles it is also possible to adjust the release position. The release process is initiated by contacting the textile with a liquid, e. G., Water, body fluids or other liquids. If it is desired to begin this process as soon as the textile is introduced into the wet environment, it is essential to use a very tight textile structure, and in these structures the sheath will also begin to tear even in small amounts of absorbed liquid. In a less tight structure there is a delayed release initiation until the environment contains an amount of liquid that will swell the fiber after absorption into the fiber. The core release rate and total release time depend on the amount of rupture in the cis. The longer the distance between the two ruptures, the longer the time it takes for the core to "flow out" from the sheath. The amount of ruptures, the spacing of each rupture, can be specifically influenced by a combination of closely intersected and rarely crossed areas in the textile, i. E., The braiding density in braided textile or the knitted textile The stitch density can be influenced by a change in the stitch density in the region of the stitch density. Then, the sheath rupture and the core release occur only at the tight position of the textile, and these ruptures gradually release the core from the sparse segment. The release rate can also be influenced by the core composition of the fibers of the present invention. Cores made with native HA are released more rapidly and cores made with acylated HA with a degree of substitution of 5% to 29%, preferably 10% to 20%, are released more slowly. In this way, the total release period can be adjusted in the range of tens of minutes to several tens of hours. If the fiber core contains an active agent, the active agent is released along with the core. The total amount of active agent released then varies according to the concentration of active agent in the fiber core, the mass ratio of core-sheath, and the total amount of fibers in the textile sample that fill the function of the active carrier. The fibers of the present invention can be variably spread over a range of textiles (similar to color patterns made with different yarns) and the effect of the core or the contained active agent is targeted to the treated tissue, which is the desired location . The fibers can be concentrated into a range of areas (e.g., center or periphery) or laterally (back or front) into a specific area of the textile pattern.

As mentioned above, both the core and sheath of the present invention may contain an active agent, for example a pharmaceutical ingredient or an inorganic particle. The type and concentration of the active agent in the core and / or sis of the fiber of the present invention may differ depending on the application of the textile of the present invention. Examples are shown in Table 6:

Table 6. Examples of active agents.

The use options of the textile of the present invention have different release carinities:

For example, fast hemostatic release within a few hours may be used to reduce tissue bleeding during or immediately after surgery.

For example, a medium fast release of local anesthetic within a few hours may be used to reduce pain or post-operative pain.

Slow antiseptic release within 1 to 2 days may be used for dressing against infectious chronic wounds.

Slow fibrinolytic release within a few days can support the effect of an adhesive.

The braided textile, woven textile, knitted textile or nonwoven textile of the present invention can be used in the fields of medicine, tissue engineering and controlled release systems.

Justice

The term " single fiber " means a fiber consisting solely of one morphological component.

The term " lower alcohol " means a C ₁ -C ₆ alkanol.

The term " core-cis fiber " means a two-component (two component) fiber composed of a fiber core and a sheath.

The term " degree of substitution " is the molar amount of 100% * coupled acyl / molar amount of all polysaccharide dimers.

The term " corresponding fiber diameter " means a diameter of a circle having the same area as the cross-sectional area of the fibers of the present invention.

The term " hyaluronan ", " HA " or " native hyaluronan " means hyaluronic acid and / or its salts which can be processed or processed in the form of core- cis fiber of the present invention.

The term " C ₁₁ -C ₁₈ acylated hyaluronan " or " C ₁₁ -C ₁₈ acylated HA " refers to acylated hyaluronan using C ₁₁ -C ₁₈ fatty acid in the hydroxyl group of hyaluronan .

The term " co-extruded " means simultaneously extruding two different polymer solutions into a coagulation bath through a two-way coaxial spinneret.

The term " monofilament " means a single endless fiber.

The term " spinning yarn " is understood to be a single endless fiber (monofilament), a bundle of parallel fibers or a twisted bundle of fibers.

The term " twisted bundle of fibers " means a bundle having at least one twist per 1 m in two or more parallel fibers forming the bundle.

The term " staple fiber " means a fiber set made by cutting or tearing endless fibers. The staple fibers may have different lengths (ranging from 3 to 150 mm).

The term " fineness " is expressed in [tex] units and is expressed in grams (1 tex = 1 g / km) of a fiber or yarn weight of 1 kilogram.

The term " inert material " means a non-absorbable biocompatible polymer.

The term " rupture effect " means that an acylated hyaluronan having a degree of substitution of 30 to 80%, preferably 40 to 60% in the core-cis fiber due to mechanical stresses caused by fiber swelling in the textile structure Means that the core made of the original hyaluronan or acylated hyaluronan having a degree of substitution of 5 to 29%, preferably 10 to 20%, is released.

The term " braiding angle " means the angle between the longitudinal axis of the yarn yarn and the braiding textile, or the half angle between the yarns crossed with respect to the braiding direction.

The term " braiding density " refers to a continuous yarn transfer (in tubular textiles) from the face to the back (in flat textiles) or from the outer to the inner surface per cm of the length of the braided textile, .

The term " fabric sett " refers to the number of warp or weft yarns per cm width or length of woven textile.

The term " wale density " means the number of wales of the knitted textile per 1 dm width of the knitted textile.

The term " nano-micelle composition " refers to a nano-capsule having dimensions of 20 to 100 nm, made of acylated hyaluronan formed in a micelle structure and carrying the active agent to the core.

Figure 1 a shows the centric arrangement of the core and sheath in the fiber. The core is illustratively drawn out of the sheath.
Fig. 1b shows core-cis fiber containing magnetic nano-particles prepared according to Example 6. Fig.
Figure 2a shows a braided textile composed of sixteen core-cis fibers of the present invention with filled fibers inserted before being soaked in water. The fibers were prepared according to the manufacturing method mentioned in Example 6 and processed by braiding according to Example 18a.
Figure 2b shows the same bleached textile as the textile of Figure 2a, hyaluronan from the core and release of the active agent and air-drying after being soaked in water.
3 shows the structure of the braided tube of Example 17a.
Figure 4 is a core-cis fiber fabricated in the form of a needled textile of Example 22;
5 is a core-cis fiber processed to the warp knitted textile of Example 23. Fig.
Figure 6a is a braided web with filled fibers of Example 18c.
Fig. 6b is a view showing the filament yarn having the filled fibers of Example 18c in detail; Fig.

Example

The molar mass of hyaluronan was confirmed using HPLC Shimadzu with light scattering detector midiDAWN Watt Technologies (the so-called SEC-MALLS method). Unless otherwise stated, the stated molecular mass is the average mass.

A photograph of the core-cis fiber was taken on a scanning electron microscope:

One) It is a Tescan VEGA II LSU with a wolfram cathode and a maximal resolution of 3 nm. The acceleration voltage of the primary beam was 5 kV and images were taken under high vacuum at a working distance of 3-4 mm.

2) ZEISS ULTRA PLUS equipped with a Schottky cathode. The microscope reaches a maximum resolution of 0.8 nm at 30 kV for the STEM detector. The accelerating voltage of the primary beam was 5 kV, the working distance was 4.6 mm, the current was 40 pA, and images were captured using an InLens SE detector.

Example 1

From sodium hyaluronate and palmitoyl hyaluronan, core-sheath Manufacture of fibers

For the preparation of the fiber core, 0.49 g of sodium hyaluronate (MW 1.57 x 10 ⁶ g / mol) was dissolved in 32.5 mL of demineralized water. A sheath solution was prepared by mixing 1.65 g of palmitoyl hyaluronane (Mw 2.4x10 ⁵ g / mol, 28% substitution) with 15 mL of demineralized water and 15 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a 2-way coaxial spinneret into a coagulation bath using a pair of dosage systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a 0.4 m long bath at a speed of 0.6 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol.

The volume ratio of core and sheath was 1: 3.5. The fiber fineness was 19 tex, the strength was 1.46 N, and the elongation at break was 12.3%.

Example 2

Preparation of Core-Cis Fiber from Palmitoyl Hyaluronan and Sodium Hyaluronate

For the preparation of the fiber core, 1.5 g of palmitoyl hyaluronate (Mw 2.4 x 10 ⁵ g / mol, 28% substitution) was dissolved in 11 mL of demineralized water and 11 mL of propan-2-ol. A sheath solution was prepared by mixing 0.66 g of sodium hyaluronate (Mw 1.57x10 ⁶ g / mol) with 22 mL of demineralized water. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a 0.4 m long bath at a speed of 1.0 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol.

The volume ratio of core and sheath was 2.3: 1. The fiber fineness was 22 tex.

Example 3

Preparation of core-cis fiber from sodium hyaluronate and stearoyl hyaluronan

For the preparation of the fiber core, 0.49 g of sodium hyaluronate (MW 1.57 x 10 ⁶ g / mol) was dissolved in 32.5 mL of demineralized water. A sheath solution was prepared by mixing 0.95 g of stearoyl hyaluronane (Mw 1.3x10 ⁶ g / mol, degree of substitution 35%) with 15 mL of demineralized water and 15 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.6 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol.

The volume ratio of core and sheath was 1: 2.1. The fiber fineness was 15 tex.

Example 4

Preparation of core-cis fiber from sodium hyaluronate and palmitoyl hyaluronan while adding octenidine dihydrochloride into the fiber core

For the production of the fiber core, 0.375 g of sodium hyaluronate (MW 1.57 x 10 ⁶ g / mol) was dissolved in 21.6 mL of demineralized water. 10 mg of octenidine dihydrochloride was added to the solution. A sheath solution was prepared by mixing 0.88 g of palmitoyl hyaluronane (Mw 2.4x10 ⁵ g / mol, degree of substitution 27%) with 11 mL of demineralized water and 11 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a 0.4 m long bath at a speed of 1.0 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol.

The volume ratio of core and sheath was 1: 2.3. The fiber fineness was 20 tex.

Example 5

Preparation of core-cis fiber from sodium hyaluronate and palmitoyl hyaluronan, while adding dexamethasone sodium phosphate

For the preparation of the fiber core, 0.3 g of sodium hyaluronate (MW 1.57 x 10 ⁶ g / mol) was dissolved in 18 mL of demineralized water. 15 mg of dexamethasone sodium phosphate was added to the solution. A sheath solution was prepared by mixing 1.32 g of palmitoyl hyaluronan (Mw 2.4x10 ⁵ g / mol, 28% substitution) with 11 mL of demineralized water and 11 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.6 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol.

The volume ratio of core and sheath was 1: 3.6. The fiber fineness was 28 tex.

Example 6

Preparation of core-cis fiber from sodium hyaluronate and palmitoyl hyaluronan with magnetic nano-particles added

For the preparation of the fiber core, 0.48 g of sodium hyaluronate (MW 1.57 x 10 ⁶ g / mol) was dissolved in 32 mL of demineralized water. 8.55 a distributed magnetic nano based on the iron oxide in ethanol at a density of g.cm ^-3-7 mg particles (nano-size of the particle is 6 to 10 nm, that is covered by the triethylene glycol), and the solution Lt; / RTI > A sheath solution was prepared by mixing 2.33 g of palmitoyl hyaluronane (Mw 2.70x10 ⁵ g / mol, degree of substitution 37%) with 16 mL of demineralized water and 16 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.6 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol.

The volume ratio of core and sheath was 1: 5. The fiber fineness was 32 tex, the strength was 2.62 N, and the elongation at break was 8.1%.

Example 7

Production of core-cis fiber from sodium hyaluronate having a low molar mass and palmytoyl hyaluronan having a high molar mass

For the preparation of the fiber core, 1 g of sodium hyaluronate (Mw 3 x 10 ⁵ g / mol) was dissolved in 24 mL of demineralized water. A sheath solution was prepared by mixing 1.87 g of palmitoyl hyaluronane (Mw 6.40x10 ⁵ g / mol, degree of substitution 44%) with 17 mL of demineralized water and 17 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 250 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a 0.4 m long bath at a speed of 1.0 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol and acetone.

The volume ratio of core and sheath was 1: 1.3. The fiber fineness was 28 tex, the strength was 2.35 N, and the elongation at break was 21.1%.

Example 8

Preparation of core-cis fiber with low fineness

For the preparation of the fiber core, 0.38 g of sodium hyaluronate (Mw 1.66x10 ⁶ g / mol) was dissolved in 25 mL of demineralized water. A sheath solution was prepared by mixing 1.6 g of palmitoyl hyaluronane (Mw 2.80 x 10 ⁵ g / mol, degree of substitution 36%) with 17 mL of demineralized water and 17 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 1.3 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol and acetone.

The volume ratio of core and sheath was 1: 3. The fiber fineness was 11 tex, the strength was 1.41 N, and the elongation at break was 15.5%.

Example 9

Preparation of core-cis fiber from sodium hyaluronate and palmitoyl hyaluronan with addition of octenidine dihydrochloride in the fiber sheath

For the preparation of the fiber core, 0.45 g of sodium hyaluronate (Mw 6.80 x 10 ⁵ g / mol) was dissolved in 25 mL of demineralized water. A sheath solution was prepared by mixing 1.59 g of palmitoyl hyaluronane (Mw 2.40x10 ⁵ g / mol, degree of substitution 55%) with 17 mL of demineralized water and 17 mL of propan-2-ol. 30 mg of octenidine dihydrochloride was added to the solution. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.8 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol and acetone.

The volume ratio of core and sheath was 1: 2.5. The fiber fineness was 20 tex, the strength was 1.97 N, and the elongation at break was 15.4%.

Example 10

Preparation of core-cis fiber from sodium hyaluronate and palmitoyl hyaluronan by adding naproxen into the fiber core and adding octenidine dihydrochloride into the fiber sheath

For the preparation of the fiber core, 1.05 g of sodium hyaluronate (Mw 3 x 10 ⁵ g / mol) was dissolved in 20 mL of demineralized water. 40 mg of sodium hyaluronate derivative covalently bonded to naproxen (17% naproxen) was added to the solution. A fiber sheath solution was prepared by mixing 1.59 g of palmitoyl hyaluronan (Mw 2.40x10 ⁵ g / mol, degree of substitution 55%) with 17 mL of demineralized water and 17 mL of propan-2-ol. 30 mg of octenidine dihydrochloride was added to the solution. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 250 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a 0.4 m long bath at a speed of 1.0 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol and acetone.

The volume ratio of core and sheath was 1: 2.1. The fiber fineness was 26 tex, the strength was 1.58 N, and the elongation at break was 19.2%.

Example 11

In preparing core-cis fibers from sodium hyaluronate and palmitoyl hyaluronan, different volume ratios of demineralized water and propan-2-ol or another lower alcohol are used in the spinning solution of palmitoyl hyaluronan

For the preparation of the fiber core, 0.45 g of sodium hyaluronate (Mw 6.80x10 ⁵ g / mol) was dissolved in 25 mL demineralized water.

a) 1.60 g of palmitoyl hyaluronan (Mw 2.12x10 ⁵ g / mol, degree of substitution 58%), 17 mL of demineralized water and 17 mL of propan-2-ol (1:

b) 1.84 g of palmitoyl hyaluronan (Mw 2.12x10 ⁵ g / mol, degree of substitution 58%), 16 mL of demineralized water and 24 mL of propan-2-ol (4:

c) 1.80 g of palmitoyl hyaluronan (Mw 2.12x10 ⁵ g / mol, degree of substitution 58%), 31.5 mL of demineralized water and 3.5 mL of propan-2-ol (9: 1)

d) 1.60 g of palmitoyl hyaluronan (Mw 2.12x10 ⁵ g / mol, degree of substitution 58%), 17 mL of demineralized water and 17 mL of ethanol (1: 1)

To prepare a fiber sheath solution.

The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.8 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol and acetone.

a) The volume ratio of core and sheath was 1: 2.5. The fiber fineness was 17 tex, the strength was 1.99 N, and the elongation at break was 18.2%.

b) The volume ratio of core and sheath was 1: 2.5. The fiber fineness was 17 tex, the strength was 1.74 N, and the elongation at break was 17.8%.

c) The volume ratio of core and sheath was 1: 2.8. The fiber fineness was 17 tex.

d) The volume ratio of core and sheath was 1: 2.6. The fiber fineness was 15 tex, the strength was 1.67 N, and the elongation at break was 12.6%.

Example 12

Preparation of core-cis fiber from sodium hyaluronate and palmitoyl hyaluronan in a coagulation bath in which the ratio of lactic acid, propan-2-ol and water is different.

For the preparation of the fiber core, 0.36 g of sodium hyaluronate (Mw 1.66 x 10 ⁶ g / mol) was dissolved in 25 mL demineralized water. A fiber sheath solution was prepared by mixing 1.60 g of palmitoyl hyaluronane (Mw 2.80x10 ⁵ g / mol, degree of substitution 36%) with 17 mL of demineralized water and 17 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components.

Coagulation Bath

a) A mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4

b) A mixture of 80% D, L-lactic acid and 100% propan-2-ol and demineralized water in a volume ratio of 2: 7: 1

c) A mixture of 80% D, L-lactic acid and 100% propan-2-ol and demineralized water in a volume ratio of 0.5: 6: 3.5

.

The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 1 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol and acetone.

a) The volume ratio of core and sheath was 1: 3. The fiber fineness was 16 tex, the strength was 2.13 N, and the elongation at break was 12.8%.

b) The volume ratio of core and sheath was 1: 3. The fiber fineness was 16 tex, the strength was 1.58 N, and the elongation at break was 14.2%.

c) The volume ratio of core and sheath was 1: 3. The fiber fineness was 16 tex.

Example 13

Preparation of core-cis fiber from sodium hyaluronate and oleyl hyaluronan

For the preparation of the fiber core, 0.38 g of sodium hyaluronate (Mw 1.66x10 ⁶ g / mol) was dissolved in 25 mL of demineralized water. A fiber sheath solution was prepared by mixing 1.43 g of oleyl hyaluronan (Mw 2.8x10 ⁵ g / mol, 28% substitution) with 17 mL of demineralized water and 17 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.9 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% propan-2-ol.

The volume ratio of core and sheath was 1: 2.8. The fiber fineness was 13 tex, the strength was 1.35 N, and the elongation at break was 11.2%.

Example 14

Preparation of core-cis fiber from oleyl hyaluronan and palmitoyl hyaluronan

a) The degree of substitution in the core is 28% and the degree of substitution in the sheath is 36%.

For the preparation of the fiber core, 0.77 g of oleyl hyaluronane (Mw 2.8x10 < ⁵ > g / mol, degree of substitution 28%) was dissolved in 14 mL of demineralized water. A fiber sheath solution was prepared by mixing 1.77 g of palmitoyl hyaluronan (Mw 2.8x10 ⁵ g / mol, degree of substitution 36%) with 17 mL of demineralized water and 17 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.9 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% ethanol.

The volume ratio of core and sheath was 1: 2. The fiber fineness was 20 tex, the strength was 1.31 N, and the elongation at break was 16.9%.

b) The degree of substitution in the core is 24%, and the degree of substitution in the sheath is 50%.

For the preparation of the fiber core 0.77 g of oleyl hyaluronane (Mw 2.16x10 ⁵ g / mol, degree of substitution 24%) was dissolved in 12 mL of demineralized water and 12 mL of propan-2-ol. A fiber sheath solution was prepared by mixing 1.41 g of palmitoyl hyaluronan (Mw 2.04x10 ⁵ g / mol, degree of substitution 50%) with 15 mL of demineralized water and 15 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.9 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% ethanol and further with acetone for 4 hours.

The volume ratio of core and sheath was 1: 1.5. The fiber fineness was 20 tex, the strength was 2.03 N, and the elongation at break was 22.1%.

Example 15

Preparation of core-cis fiber from palmitoyl hyaluronan with different degrees of substitution in fiber cores and cis

a) The degree of substitution in the core is 16%, and the degree of substitution in the sheath is 75%.

For the preparation of the fiber core 0.77 g of palmitoyl hyaluronan (Mw 2.16x10 ⁵ g / mol, degree of substitution 16%) was dissolved in 14 mL of demineralized water and 14 mL of propan-2-ol. A fibrous sheath solution was prepared by mixing 1.87 g of palmitoyl hyaluronane (Mw 2.8x10 ⁵ g / mol, degree of substitution 75%) with 17 mL of demineralized water and 17 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.9 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% ethanol.

The volume ratio of core and sheath was 1: 2. The fiber fineness was 20 tex, the strength was 1.11 N, and the elongation at break was 9.5%.

b) The degree of substitution in the core is 12%, and the degree of substitution in the sheath is 60%.

0.77 g of palmitoyl hyaluronan (Mw 3.2x10 ⁵ g / mol, degree of substitution 12%) was dissolved in 12 mL of demineralized water and 12 mL of propan-2-ol for the preparation of the fiber core. A fiber sheath solution was prepared by mixing 1.41 g of palmitoyl hyaluronan (Mw 2.03x10 ⁵ g / mol, degree of substitution 60%) with 15 mL of demineralized water and 15 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.9 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% ethanol and further with acetone for 4 hours.

The volume ratio of core and sheath was 1: 1.5. The fiber fineness was 20 tex, the strength was 1.96 N, and the elongation at break was 23.0%.

c) The degree of substitution in the core is 5%, and the degree of substitution in the sheath is 44%.

0.77 g of palmitoyl hyaluronan (Mw 3.2x10 ⁵ g / mol, degree of substitution 5%) was dissolved in 12 mL of demineralized water and 12 mL of propan-2-ol for the preparation of the fiber core. A fiber sheath solution was prepared by mixing 1.41 g of palmitoyl hyaluronane (Mw 2.04x10 ⁵ g / mol, degree of substitution 44%) with 15 mL of demineralized water and 15 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.9 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% ethanol and further with acetone for 4 hours.

The volume ratio of core and sheath was 1: 1.5. The fiber fineness was 24 tex, the strength was 2.45 N, and the elongation at break was 24.3%.

Example 16

Preparation of core-cis fiber from sodium hyaluronate and oleyl hyaluronan while adding micelles containing the fluorescent agent into the fiber core

For the preparation of the fiber core, 0.38 g of sodium hyaluronate (Mw 1.66x10 ⁶ g / mol) was dissolved in 25 mL of demineralized water. 7.6 mg of an aqueous solution of a polysaccharide-based nano-micelle composite containing dye nile red (solution concentration 2% by weight) was added to the solution. A fiber sheath solution was prepared by mixing 1.43 g of oleyl hyaluronan (Mw 2.8x10 ⁵ g / mol, 28% substitution) with 17 mL of demineralized water and 17 mL of propan-2-ol. The resulting solution was degassed and co-extruded through a two-way coaxial spinneret into the coagulation bath using a pair of addition systems. The extrusion rate was 200 μL.min ^-1 for both components. The coagulation bath was prepared with a mixture of 80% D, L-lactic acid and 100% propan-2-ol in a volume ratio of 1: 4. The resulting core-cis fiber was passed through a bath of 0.4 m length at a speed of 0.9 m.min ^-1 and pulled out continuously by a winding roller. The fibers were then washed with 100% 100% propan-2-ol and acetone.

The volume ratio of core and sheath was 1: 2.8. The fiber fineness was 14 tex, the strength was 1.49 N, and the elongation at break was 16.6%.

Example 17

Fabrication of braided textile from core-cis fiber based on hyaluronan

a) Fabrication of braided tubes from hyaluronan-based core-cis fiber

A yarn made from single core-cis fiber (monofilament) derived from palmitoyl hyaluronan and sodium hyaluronate containing magnetic nano-particles prepared in accordance with Example 6 was wound on a 16 bobbin using a winding machine, , And the blade body set was machined using a STEEGER horizontal baling machine with 16 bobbins. The winding speed was 30 m / min and the braiding head speed was 50 rpm. The braiding density of the braided tube produced from 16 monofilaments / yarns in a twill was 13 cm ^-1 , the braiding angle was 30 °, and the diameter was 1.25 mm.

b) Manufacture of braided yarn from blend yarn

First, a spun yarn was prepared from a bundle of two fibers (monofilaments): a single core-cis fiber derived from palmitoyl hyaluronan and sodium hyaluronate containing magnetic nano-particles prepared according to Example 6, Lt; / RTI > fibers having a diameter of 0.08 mm and a fineness of 5.2 tex. Spun yarns were fabricated by grouping these monofilaments during rewinding on a STEEGER winding machine. The winding speed was 27 m / min and the tensile force was 8 cN. Eight bobbins with non-winding blends were gradually made. The fineness of the yarn was 37 tex. The yarn was then processed using a STEEGER horizontal baling machine with a braid body set of 8 bobbins. The braiding head speed was 30 rpm. The resulting braided density of the resultant braided yarn made of eight yarns was 10 cm ^-1 , the braiding angle was 20 °, and the diameter was 0.9 mm.

Example 18

Preparation of braided tubes from core-cis fiber based hyaluronan containing filled fibers

a) PLLA filled fibers having a diameter of 0.076 mm

In the preparation of the braided tube according to the method of Example 17a, a bundle consisting of 30 polylactic acid (PLLA) filled fibers having a diameter of 0.076 mm of Luxilon was inserted into the hollow. The generated braided tube had a braiding density of 13 cm ^-1 , a braiding angle of 30 °, and a diameter of 1.25 mm. The resulting tube was immersed in water, at which time the fibers swelled for a few minutes, their cisum started to rupture, and the active agent release from the core after 10 minutes. Four hours later, the core was poured out completely.

b) Polyester filled fibers having a diameter of 0.018 mm

In the production of the braided tube according to the method of Example 17b, a multifilament made of 200 polyester fibers with a diameter of 0.018 mm was inserted into the hollow. The produced braided tube had a braiding density of 10 cm ^-1 , a braiding angle of 28 °, and a diameter of 0.95 mm.

c) Polycaprolactone filled fibers (nano-fibers) having a diameter of 0.00054 mm

In the preparation of the braided tube according to the method of Example 17b, the surface was made of a nano-fiber layer of polycaprolactone (Mw 8.0x10 ⁴ g / mol; the nano-fiber layer was prepared using the electrostatic spinning method on the device 4SPIN) Was inserted into the hollow. The nano-fiber diameter was 0.00054 mm. The produced braided tube had a braiding density of 10 cm ^-1 , a braiding angle of 31 °, and a diameter of 1.5 mm.

Example 19

Fabrication of core-cis fiber spun yarns based on hyaluronan

a) Simple spinning yarn of 60 tex

Three monofilaments of core-cis fiber (fibers made according to Example 1) from sodium hyaluronate and palmitoyl hyaluronan were fed on a ring-twisting machine at a feed rate of 8 m / min And twisted at a spindle rotation speed of 1000 min <" ¹ >. The fineness of the resulting yarn was 60 tex and the twist was 125 m ^-1 .

b) The plied yarn of fineness of 300 tex,

Three monofilaments of core-cis fiber (fibers made according to Example 6) from sodium hyaluronate and palmitoyl hyaluronan were placed on a ring-twisting machine at a feed rate of 9 m / min and at 1000 min ^-1 Twisted at the spindle rotational speed. The fineness of this simple spinning yarn was 100 tex and the left twist was 110 m ^-1 . These three simple yarns were then grouped and twisted at a feed rate of 12 m / min and a spindle rotational speed of 1000 min ^-1 on a ring-twisting machine. The fineness of the generated sum yarn was 300 tex and the right twist was 85 m ^-1 .

Example 20

Manufacture of blends from core-cis fiber and PLLA fiber based on hyaluronan

One monofilament of core-cis fiber (fiber prepared according to Example 12b) originating from native hyaluronan and palmytoyl hyaluronan and two monofilaments of polylactic acid (PLLA) Twisted at a feed rate of 8 m / min on a twisting machine and a spindle rotational speed of 1000 min < ^-1 >. The fineness of the resulting yarn was 30 tex and the twist was 125 m ^-1 .

Example 21

Preparation of braided tubes from blends containing core-cis fiber and PLLA fibers based on hyaluronan

The yarn prepared according to Example 20 was rewound to 8 bobbins using a winding machine and then the braid body set was processed on a STEEGER horizontal baling machine with 8 bobbins. The winding speed was 30 m / min and the braiding body speed was 70 rpm. The braiding density of the braided yarn manufactured from eight yarns in twill was 15 cm ^-1 , the braiding angle was 30 °, and the diameter was 0.8 mm.

Example 22

Preparation of a weft-knitted textile containing core-cis fibers based on hyaluronan

The yarn produced in accordance with Example 19 was wound on both sides on a weft-knitting machine (gauge 10 in a needle / inch, driven by a semi-production hand, skipping the needles one by one) Further textiles were processed with knitted textiles. The density of the resultant knitted textile was 8 wale / cm and 4 courses / cm.

Example 23

Preparation of warp knitted textile containing core-cis fibers based on hyaluronan

The yarn produced according to Example 19 was further texturized in the form of a cross-section nylatetail in a tricot pattern on a warp-knitting machine-COMEZ raschel machine (at 12 needle / inch gauge). The density of the produced knitted textile was 4 wale / cm and 5 course / cm.

Claims (35)

An endless fiber in the form of a core-sheath, based on hyaluronan or its C ₁₁ -C ₁₈ acylated derivatives,
The fibers comprising a combination of hyaluronan and an acylated derivative thereof or a combination of acylated derivatives thereof,
Wherein the core and sheath of the fibers are present in any one of the following arrangements:
A) the core comprises hyaluronic acid or a salt thereof, wherein the cis comprises an arrangement comprising C ₁₁ -C ₁₈ acylated hyaluronan;
B) the core comprises C ₁₁ -C ₁₈ acylated hyaluronan, the cis comprises an array comprising hyaluronic acid or a salt thereof;
C) a core is C ₁₁ -C ₁₈ Ah comprises I to the acylated hyaluronic, sheath difference is different from a C ₁₁ -C ₁₈ ah acylated hyaluronic the core I and the C ₁₁ -C ₁₈ C ₁₁ -C ₁₈ acyl Wherein the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan in the cis is the same or different from the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan in the core; or
D) core comprises a C ₁₁ -C ₁₈ acylated hyaluronan, wherein the sheath comprises a different C ₁₁ -C ₁₈ acylated hyaluronan, which differs in the degree of substitution from the C ₁₁ -C ₁₈ acylated hyaluronan of the core An array containing Ronan. The method according to claim 1,
Characterized in that the C ₁₁ -C ₁₈ acylated hyaluronan is acylated in a primary alcohol of N -acetyl-glucosamine. 3. The method according to claim 1 or 2,
The molar mass of the C ₁₁ -C ₁₈ acylated hyaluronan ranges from 1 × 10 ⁵ g / mol to 7 × 10 ⁵ g / mol, preferably from 2 × 10 ⁵ g / mol to 3 × 10 ⁵ g / mol ≪ / RTI > 4. The method according to any one of claims 1 to 3,
Characterized in that the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan in the sequence A or the sequence B is in the range of 5% to 80%, preferably 30% to 60%. 4. The method according to any one of claims 1 to 3,
The substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the core of the array C is in the range of 5% to 80%, preferably 5% to 29%, more preferably 10% to 20% , The substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan contained in the sheath of arrangement C is in the range of 5% to 80%, preferably 30% to 80%, more preferably 40% to 60% ; or
Wherein contained within the core of the array D C ₁₁ -C ₁₈ Oh I is substituted by a misfire of hyaluronic 5% to 29%, preferably from 10% to 20%, and wherein the arrangement included in the system of the D C ₁₁ - Characterized in that the substitution degree of the C ₁₈ acylated hyaluronan is in the range of 30% to 80%, preferably 40% to 60%. 6. The method according to any one of claims 1 to 5,
Wherein the C ₁₁ -C ₁₈ acylated hyaluronan is selected from the group consisting of palmitoyl hyaluronan, stearoyl hyaluronan, or oleyl hyaluronan. The method according to any one of claims 1 to 4 or 6,
Wherein the hyaluronic acid and / or its salt molar mass of 1x10 ⁵ g / mol to 2x10 ⁶ g / mol, preferably 8x10 ⁵ g / mol to a range of 1.8x10 ⁶ g / mol,
Characterized in that the salt of hyaluronic acid is selected from the group consisting of alkali metal ions, alkaline earth metal ions, preferably Na ⁺ , K ⁺ , Ca ^{2 +} or Mg ^{2 +} . 8. The method according to any one of claims 1 to 7,
Characterized in that the fiber fineness is in the range of 10 tex to 40 tex, preferably 15 tex to 35 tex, more preferably 22 tex to 28 tex. 9. The method according to any one of claims 1 to 8,
Wherein the core: sheath has a volume ratio in the range of 3: 1 to 1: 6, preferably 1: 3 to 1: 5, more preferably 1: 4. 10. The method according to any one of claims 1 to 9,
Characterized in that the fibers comprise at least one activator. 11. The method of claim 10,
Wherein the core and the sheath both comprise one or more of the same or different active agents. The method according to claim 10 or 11,
Characterized in that the active agent is selected from the group consisting of antimicrobial agents, disinfectants, antibiotics, anti-inflammatory agents, hemostats, anesthetics, cytostatics, hormones, immunomodulators, immunosuppressants or contrast agents, preferably magnetic nano-particles. 13. The method according to any one of claims 1 to 12,
Fibers for use in the manufacture of yarns, braided textile, woven textile, knitted textile or nonwoven textile. 14. A process for producing a fiber according to any one of claims 1 to 13,
The above-
A first spinning solution comprising hyaluronic acid or a salt thereof in water in a concentration range of 1 wt% to 8 wt%, and a second spinning solution containing 2 wt% or more of C ₁₁ -C ₁₈ acylated hyaluronan in a mixture of water and a lower alcohol Wherein the water content is in the range of 30 v / v% to 90 v / v%, the lower alcohol content is in the range of 10 v / v% to 70 v / v%
After the preparation, both the first spinning solution and the second spinning solution contain from 2% to 40% by weight of an organic acid, preferably lactic acid, at least 50% by weight of a lower alcohol, preferably ethanol, Propane-2-ol and from 2% to 48% by weight of water to form fibers of arrangement A or arrangement B,
Characterized in that the fibers are washed with a lower alcohol and then dried. 14. A process for producing a fiber according to any one of claims 1 to 13,
The above-
In a mixture of water and lower alcohols C ₁₁ -C ₁₈ Oh I with a different hyaluronic misfire in the first spinning solution, and a mixture of water and a lower alcohol containing a concentration ranging from 2% to 8% by weight of C ₁₁ -C ₁₈ acylated hyaluronan in a concentration ranging from 2% by weight to 8% by weight, wherein the water content in both solutions is from 30 v / v% to 90 v / v%, the lower alcohol content is in the range of 10 v / v% to 70 v / v%
After the preparation, both the first spinning solution and the second spinning solution contain from 2% to 40% by weight of an organic acid, preferably lactic acid, at least 50% by weight of a lower alcohol, preferably ethanol, Propane-2-ol and from 2% to 48% by weight of water to form fibers of arrangement C or arrangement D,
Characterized in that the fibers are washed with a lower alcohol and then dried. 16. The method according to claim 14 or 15,
Characterized in that the first spinning solution and / or the second spinning solution comprises an activator. 16. The method according to claim 14 or 15,
Characterized in that said first spinning solution and / or said second spinning solution comprises an acylated hyaluronan-based nano-micelle composition comprising said active agent. A staple fiber made from the fiber according to any one of claims 1 to 13. A non-woven textile made from the staple fiber according to claim 18. 14. A yarn made from at least one fiber according to any one of claims 1 to 13. 21. The method of claim 20,
Characterized in that the yarn is formed of a fiber bundle comprising 2 to 10 fibers, preferably 3 to 6 fibers. 22. The method of claim 21,
Characterized in that the yarn is in the form of a twisted bundle of fibers. As yarns formed of two or more fibers,
Wherein the at least one fiber is a fiber according to any one of claims 1 to 13,
Wherein the at least one fiber is selected from the group consisting of fibers of other biodegradable materials,
The biodegradable material may be selected from the group consisting of polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, polycaprolactone, polydioxanone or polyhydroxyalkanoate, preferably polylactic acid, or polylactic acid and polyglycol ≪ / RTI > acid copolymers. 24. The method according to any one of claims 20 to 23,
Characterized in that the fineness of the yarn is in the range of 10 tex to 400 tex, preferably 30 tex to 100 tex. As braided textile, woven textile or knit textile,
Wherein the textile comprises at least one yarn according to any one of claims 20-24. 26. The method of claim 25,
Wherein the textile is made of a yarn according to any one of claims 20 to 24. 27. The method of claim 25 or 26,
In the case of the arrangement A, the degree of substitution of the C ₁₁ -C ₁₈ acylated hyaluronan is in the range of 30% to 80%, preferably, in the case of the arrangement A, the fiber core and the sheath in the yarn are present in the arrangement A, 40% to 60%, and in the case of the arrangement C or the arrangement D, the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan in the core is in the range of 5% to 29%, preferably 10% to 20% , And the substitution degree of the C ₁₁ -C ₁₈ acylated hyaluronan in the sheath is in the range of 30% to 80%, preferably 40% to 60%. Knitted Textile. 28. The method according to any one of claims 25 to 27,
Wherein the textile is present in the form of a linear, flat or tubular textile. ≪ RTI ID = 0.0 > 11. < / RTI > 29. The method according to any one of claims 25 to 28,
Characterized in that the textile comprises at least eight yarns and comprises at least one filler fiber in the textile. 30. The method of claim 29,
Characterized in that the diameter of the filled fibers ranges from 0.0001 mm to 1 mm, preferably from 0.01 mm to 0.1 mm. 32. The method according to claim 29 or 30,
Wherein the filled fibers are selected from the group consisting of hyaluronic acid or derivatives thereof, polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, polycaprolactone, polydioxanone, polyhydroxyalkanoate, polyethylene, polypropylene, polyether Is formed of a polymer selected from the group consisting of esters, polyamides or polyesters, preferably polylactic acid, or copolymers of polylactic acid and polyglycolic acid. 32. The method according to any one of claims 25 to 31,
When the braiding density of the yarn is in the range of y cm (cm) to 10 cm (cm), when the yarn fineness is x tex, as mentioned in the following table, while the braiding angle is 20 ° or more, ^-1 or more, preferably, bonded textile breaker characterized in that the application to be greater than or equal to z cm ^-1.

29. The method according to any one of claims 25 to 28,
Characterized in that when the yarn fineness is a tex, the fabric set is applied at b cm < ^-1 > or more, preferably at least c cm < ^-1 >, as mentioned in the table below.

29. The method according to any one of claims 25 to 28,
Characterized in that when the yarn fineness is e tex, the wale density is applied as f cm ^-1 or more, preferably g cm ^-1 or more, as mentioned in the table below.

34. A nonwoven textile according to claim 19 and a braided, woven or knit textile according to any one of claims 25 to 34 for use in medicinal, tissue engineering and controlled release system areas.

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